Diffusion Biased by a Soft Neck Linker Regulates Kinesin Stepping

Abstract

Conventional kinesin is a high-performance motor that moves primarily toward the plus end of microtubules and occasionally toward the opposite direction. The physical mechanism of this directional stepping remains unclear. Here we develop a kinetic twocycle model incorporating kinesin forward and backward stepping, in which the neck linker zippering and ATP catalysis process are conserved in backward steps. This model is quantitatively validated by a variety of experimental data, including load dependence of velocity, stepping ratio, and dwell time. The physical mechanism of kinesin stepping regulated by a biased diffusion process is identified by analyzing the load dependence and relevant thermodynamic properties of the model. Furthermore, the model suggests the kinesin directionality is optimized resulting from fulfilling a thermodynamic constraint. Our modeling provides a chemomechanical coupling mechanism that connects the flexibility of the neck linker zippering effect for direction rectification and the measured performance into a consistent frame.

Synthesis of theories on cellular powering, coherence, homeostasis and electro‐mechanics: Murburn concept and evolutionary perspectives

“…B : The hand over hand model for the movement of transport movement of kinesin (Vale et al, 1996) toward the plus end of microtubules (made of tubulin), although supported by evidence, appears too deterministic and does not account for entropy or water‐based effects. A diffusion‐biased movement aided by the soft neck linker was recently proposed (Xu et al, 2021).…”

Synthesis of theories on cellular powering, coherence, homeostasis and electro-mechanics: Murburn concept & evolutionary perspectives

“…The hand over hand model for the movement of transport movement of kinesin (Vale et al, 1996) towards the plus end of microtubules (made of tubulin), although supported by evidence, appears too deterministic and does not account for entropy or water-based effects. A diffusion biased movement aided by the soft neck linker was recently proposed (Xu et al, 2021).…”